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organisms have evolved mechanisms to cope with a variety of stress situations. One type of stress response is triggered by heavy metals, such as zinc, copper and cadmium (for convenience, the terms zinc, copper and cadmium are also used here to denote Zn2+, Cu2+ and Cd2+, respectively). Metallothioneins (MTs), small, cysteine-rich proteins, play an important role in metal homeostasis and detoxification due to their ability to bind different heavy metal ions (1–3). In the mouse, there are four metallothionein genes, designated as Mt1 to Mt4. Basal, as well as heavy metal-induced, expression of Mt1 and Mt2 is mediated by metal-responsive transcription factor 1 (MTF-1) (4–7). This zinc finger protein recognizes short cis-acting DNA sequences, termed metal response elements (MREs; core consensus sequence TGCRCNC), which are present in the promoters of target genes (8,9). MTF-1 is conserved in evolution, and homologs have been characterized in the mouse (10), humans (11), Drosophila (12–14) and fish (15,16)."}

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{"project":"craft-ca-core-dev","denotations":[{"id":"T717","span":{"begin":4,"end":13},"obj":"NCBITaxon:1"},{"id":"T718","span":{"begin":256,"end":260},"obj":"CHEBI:29105"},{"id":"T719","span":{"begin":262,"end":266},"obj":"CHEBI:29036"},{"id":"T720","span":{"begin":271,"end":275},"obj":"CHEBI:48775"},{"id":"T721","span":{"begin":379,"end":390},"obj":"GO:0042592"},{"id":"T722","span":{"begin":395,"end":409},"obj":"GO:0098754"},{"id":"T723","span":{"begin":461,"end":465},"obj":"CHEBI:24870"},{"id":"T724","span":{"begin":480,"end":485},"obj":"NCBITaxon:10088"},{"id":"T725","span":{"begin":518,"end":523},"obj":"SO:0000704"},{"id":"T726","span":{"begin":539,"end":542},"obj":"PR:000010925"},{"id":"T727","span":{"begin":546,"end":549},"obj":"PR:000010706"},{"id":"T728","span":{"begin":590,"end":600},"obj":"GO:0010467"},{"id":"T729","span":{"begin":604,"end":607},"obj":"PR:000010925"},{"id":"T730","span":{"begin":612,"end":615},"obj":"PR:000010704"},{"id":"T731","span":{"begin":631,"end":670},"obj":"PR:000010717"},{"id":"T732","span":{"begin":672,"end":677},"obj":"PR:000010717"},{"id":"T733","span":{"begin":797,"end":806},"obj":"SO:0000993"},{"id":"T734","span":{"begin":851,"end":860},"obj":"SO:0000167"},{"id":"T735","span":{"begin":871,"end":876},"obj":"SO:0000704"},{"id":"T736","span":{"begin":884,"end":889},"obj":"PR:000010717"},{"id":"T737","span":{"begin":921,"end":929},"obj":"SO:0000853"},{"id":"T738","span":{"begin":961,"end":966},"obj":"NCBITaxon:10088"},{"id":"T739","span":{"begin":973,"end":979},"obj":"NCBITaxon:9606"},{"id":"T740","span":{"begin":986,"end":996},"obj":"NCBITaxon:7215"}],"text":"All organisms have evolved mechanisms to cope with a variety of stress situations. One type of stress response is triggered by heavy metals, such as zinc, copper and cadmium (for convenience, the terms zinc, copper and cadmium are also used here to denote Zn2+, Cu2+ and Cd2+, respectively). Metallothioneins (MTs), small, cysteine-rich proteins, play an important role in metal homeostasis and detoxification due to their ability to bind different heavy metal ions (1–3). In the mouse, there are four metallothionein genes, designated as Mt1 to Mt4. Basal, as well as heavy metal-induced, expression of Mt1 and Mt2 is mediated by metal-responsive transcription factor 1 (MTF-1) (4–7). This zinc finger protein recognizes short cis-acting DNA sequences, termed metal response elements (MREs; core consensus sequence TGCRCNC), which are present in the promoters of target genes (8,9). MTF-1 is conserved in evolution, and homologs have been characterized in the mouse (10), humans (11), Drosophila (12–14) and fish (15,16)."}

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